Ignite Creation Date:
2025-12-24 @ 10:40 PM
Ignite Modification Date:
2026-01-06 @ 9:07 AM
Study NCT ID:
NCT00838435
Status:
COMPLETED
Last Update Posted:
2020-12-22
First Post:
2009-02-05
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D010661', 'term': 'Phenylketonurias'}], 'ancestors': [{'id': 'D020739', 'term': 'Brain Diseases, Metabolic, Inborn'}, {'id': 'D001928', 'term': 'Brain Diseases, Metabolic'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D000592', 'term': 'Amino Acid Metabolism, Inborn Errors'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C003402', 'term': 'sapropterin'}, {'id': 'C046978', 'term': 'phenoptin'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'MEDINFO@bmrn.com', 'phone': '651.523.0310', 'title': 'Joshua Lilienstein/Medical Director, Global Medical Affairs', 'organization': 'BioMarin Pharmaceutical Inc.'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'Up to 7 years', 'eventGroups': [{'id': 'EG000', 'title': 'Safety Population', 'description': 'All subjects who enrolled in the study (Full Analysis Set) and received any study drug.', 'otherNumAtRisk': 95, 'deathsNumAtRisk': 95, 'otherNumAffected': 90, 'seriousNumAtRisk': 95, 'deathsNumAffected': 0, 'seriousNumAffected': 12}], 'otherEvents': [{'term': 'Lymphadenopathy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 13}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Ear pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 7}], 'organSystem': 'Ear and labyrinth disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Conjunctivitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 9}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Myopia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 5}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Abdominal discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 8}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 14}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Abdominal pain upper', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 17}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 11}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 39}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 5}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Teething', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 5}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Toothache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 6}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 53}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 6}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 56}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Seasonal allergy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 11}], 'organSystem': 'Immune system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Bronchitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 11}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Conjunctivitis infective', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 7}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Croup infectious', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 9}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Ear infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 26}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Gastroenteritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 28}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Gastroenteritis viral', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 11}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Hand-foot-and-mouth disease', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 7}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Influenza', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 20}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Lower respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 5}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 42}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Otitis media', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 22}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Pharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 8}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Pharyngitis streptococcal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 19}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 6}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Rhinitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 6}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Sinusitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 13}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Streptococcal infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 7}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 55}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Urinary tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 6}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Viral infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 18}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Fall', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 6}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Laceration', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 7}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Ligament sprain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 5}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Procedural pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 5}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Red blood cell sedimentation rate increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 5}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Decreased appetite', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 11}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 7}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Pain in extremity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 5}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Skin papilloma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 5}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 25}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Anxiety', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 6}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Attention deficit/hyperactivity disorder', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 9}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 43}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Nasal congestion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 16}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Oropharyngeal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 17}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Rhinorrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 30}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Dry skin', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 6}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Eczema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 5}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 15}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Urticaria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 5}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}], 'seriousEvents': [{'term': 'Phenylketonuria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 1}], 'organSystem': 'Congenital, familial and genetic disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Colitis ulcerative', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Croup infectious', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Gastroenteritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Airway complication of anaesthesia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Concussion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Injury', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Convulsion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 2}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Autism spectrum disorder', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Diet noncompliance', 'stats': [{'groupId': 'EG000', 'numAtRisk': 95, 'numAffected': 1}], 'organSystem': 'Social circumstances', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Full-Scale Intelligence Quotient (FSIQ) Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '63', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Kuvan 20 mg/kg Once Daily', 'description': 'A dose of 20 mg/kg dissolved in water or apple juice, administered once daily orally, with food.\n\nPart 2 (7 years): Part 1 determined that 71 subjects were Kuvan responders, defined as a 30% average reduction in blood Phe concentration during the first 4 weeks .This included 8 subjects who had Phe reductions less than 30% but were granted exemptions to participate in Part 2 of the study.\n\nSixty-five of these 71 subjects were enrolled in Part 2. All 65 subjects met the minimum required FSIQ test score of ≥80 at baseline (Month 2).'}], 'classes': [{'title': 'FSIQ Baseline', 'denoms': [{'units': 'Participants', 'counts': [{'value': '63', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '101.06', 'spread': '14.039', 'groupId': 'OG000'}]}]}, {'title': 'FSIQ Month 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '59', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '103.64', 'spread': '13.202', 'groupId': 'OG000'}]}]}, {'title': 'FSIQ Month 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '58', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '104.69', 'spread': '11.697', 'groupId': 'OG000'}]}]}, {'title': 'FSIQ Month 36', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '103.78', 'spread': '12.759', 'groupId': 'OG000'}]}]}, {'title': 'FSIQ Month 48', 'denoms': [{'units': 'Participants', 'counts': [{'value': '48', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '104.25', 'spread': '13.242', 'groupId': 'OG000'}]}]}, {'title': 'FSIQ Month 60', 'denoms': [{'units': 'Participants', 'counts': [{'value': '38', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '100.76', 'spread': '14.280', 'groupId': 'OG000'}]}]}, {'title': 'FSIQ Month 72', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '104.57', 'spread': '11.012', 'groupId': 'OG000'}]}]}, {'title': 'FSIQ Month 84', 'denoms': [{'units': 'Participants', 'counts': [{'value': '27', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '104.22', 'spread': '12.236', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Slope', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.5768', 'ciLowerLimit': '-1.6004', 'ciUpperLimit': '0.4468', 'estimateComment': 'The slope shown above is based on a 2-year window.', 'groupDescription': 'A random coefficient model was used to calculate the slope (per year) of FSIQ over the entire study period. Factors in the model included visit and testing sequence, with change in FSIQ score as the dependent variable. Random terms include both intercept and visit. The treatment was considered successful if the lower 95% confidence limit of the mean change excluded a decline of greater than 5 points over a 2-year window.', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Coefficient estimates from a random coefficient model and associated p-values.'}], 'paramType': 'MEAN', 'timeFrame': 'Assessments through 84 months.', 'description': 'Full Scale Intelligence Quotient (FSIQ) is a score derived through administration of selected subtests from age appropriate Wechsler Intelligence assessments. Weschler Preschool and Primary Scale of Intelligence (WPPSI)-III is used for children \\>30 months and ≤6 years; and Weschler Intelligence Scale for Children (WISC)-IV is used for children \\>6 years old. The outcome variable will be the FSIQ score from WPPSI-III and/or WISC-IV tests.\n\nFSIQ results can range from 40 being the lowest and 160 being the highest. Higher scores are associated with higher intelligence quotient.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy population is based on all subjects from the enrolled population who have at least 2 WPPSI/ WISC assessments.'}, {'type': 'SECONDARY', 'title': 'Number of Subjects With Adverse Events (AEs)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '65', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Part 2', 'description': 'A dose of 20 mg/kg dissolved in water or apple juice, administered once daily orally, with food.\n\nPart 2 (7 years): Sixty-five of the 71 subjects that were determined to be Kuvan responders in Part 1 were enrolled in Part 2. All 65 subjects met the minimum required IQ test score of ≥80 at baseline (Month 2).'}], 'classes': [{'title': 'Any Adverse Events (AEs)', 'categories': [{'measurements': [{'value': '65', 'groupId': 'OG000'}]}]}, {'title': 'Drug-Related Adverse Events', 'categories': [{'measurements': [{'value': '35', 'groupId': 'OG000'}]}]}, {'title': 'Any Serious Adverse Events', 'categories': [{'measurements': [{'value': '11', 'groupId': 'OG000'}]}]}, {'title': 'Drug-Related Serious Adverse Events', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}, {'title': 'Any AEs causing study discontinuation', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}, {'title': 'Drug-related AEs causing study discontinuation', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}, {'title': 'Death', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Up to 7 years', 'description': 'Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, and that does not necessarily have a causal relationship with this treatment.\n\nDrug Related Adverse all noxious and unintended responses to a medical product related to any dose. This means that a causal relationship between a medicinal product and an AE is at least a reasonable possibility, ie, the relationship cannot be ruled out.\n\nA serious adverse event (SAE) is an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Enrolled Population consists of all subjects who enter Part 2. This population involves subjects who respond to Kuvan and had a Bayley-III or IQ test score ≥80 within 6 weeks of determination of Kuvan responsiveness in Part 1. Kuvan 20 mg/kg once daily.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Growth Measurements - Height Z-Scores', 'denoms': [{'units': 'Participants', 'counts': [{'value': '63', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sapropterin Dihydrochloride', 'description': 'A dose of 20 mg/kg dissolved in water or apple juice, administered once daily orally, with food.\n\nPart 2 (7 years): Sixty-five of the 71 subjects that were determined to be Kuvan responders in Part 1 were enrolled in Part 2. All 65 subjects met the minimum required IQ test score of ≥80 at baseline (Month 2).'}], 'classes': [{'title': 'Baseline', 'denoms': [{'units': 'Participants', 'counts': [{'value': '63', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.4', 'spread': '0.97', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Week 4', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.44', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 3', 'denoms': [{'units': 'Participants', 'counts': [{'value': '61', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.1', 'spread': '0.57', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 6', 'denoms': [{'units': 'Participants', 'counts': [{'value': '59', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.1', 'spread': '0.72', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.1', 'spread': '0.73', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 18', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.78', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.71', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 30', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.1', 'spread': '0.72', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 36', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.1', 'spread': '0.71', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 42', 'denoms': [{'units': 'Participants', 'counts': [{'value': '61', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.1', 'spread': '0.73', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 48', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.2', 'spread': '0.77', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 54', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.2', 'spread': '0.78', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 60', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.2', 'spread': '0.75', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 66', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.2', 'spread': '0.77', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 72', 'denoms': [{'units': 'Participants', 'counts': [{'value': '59', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.3', 'spread': '0.78', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 78', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.2', 'spread': '0.78', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 84', 'denoms': [{'units': 'Participants', 'counts': [{'value': '50', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.2', 'spread': '0.83', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and up to 84 months', 'description': 'Z-scores of Height determined using World Health Organization(WHO) growth charts for children \\<24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months and older.\n\nA height z-score is a standardized height measure after considering important factors like age and gender, in which higher z-scores are associated with taller children. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of standard deviation (SD) unit above the 50%; and a negative value is a factor of SD unit below 50%.', 'unitOfMeasure': 'Z-score change from baseline', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Growth Measurements - Weight Z-Scores', 'denoms': [{'units': 'Participants', 'counts': [{'value': '63', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sapropterin Dihydrochloride', 'description': 'A dose of 20 mg/kg dissolved in water or apple juice, administered once daily orally, with food.\n\nPart 2 (7 years): Sixty-five of the 71 subjects that were determined to be Kuvan responders in Part 1 were enrolled in Part 2. All 65 subjects met the minimum required IQ test score of ≥80 at baseline (Month 2).'}], 'classes': [{'title': 'Baseline', 'denoms': [{'units': 'Participants', 'counts': [{'value': '63', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.4', 'spread': '0.84', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Week 4', 'denoms': [{'units': 'Participants', 'counts': [{'value': '63', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.24', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 3', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.26', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 6', 'denoms': [{'units': 'Participants', 'counts': [{'value': '61', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.36', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '63', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.1', 'spread': '0.45', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 18', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.1', 'spread': '0.59', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.1', 'spread': '0.62', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 30', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.1', 'spread': '0.68', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 36', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.1', 'spread': '0.71', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 42', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.75', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 48', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.79', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 54', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.84', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 60', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.91', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 66', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.85', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 72', 'denoms': [{'units': 'Participants', 'counts': [{'value': '59', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.77', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 78', 'denoms': [{'units': 'Participants', 'counts': [{'value': '56', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.81', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 84', 'denoms': [{'units': 'Participants', 'counts': [{'value': '50', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.85', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and up to 84 months', 'description': 'Z-scores of Weight determined using World Health Organization(WHO) growth charts for children \\<24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months or older.\n\nA weight z-score is a standardized weight measure after considering important factors like age and gender, in which higher z-scores are associated with heavier children. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of SD unit above the 50%; and a negative value is a factor of SD unit below 50%.', 'unitOfMeasure': 'Z-score change from baseline', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Growth Measurements - Head Circumference Z-Scores', 'denoms': [{'units': 'Participants', 'counts': [{'value': '33', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sapropterin Dihydrochloride', 'description': 'A dose of 20 mg/kg dissolved in water or apple juice, administered once daily orally, with food.\n\nPart 2 (7 years): Sixty-five of the 71 subjects that were determined to be Kuvan responders in Part 1 were enrolled in Part 2. All 65 subjects met the minimum required IQ test score of ≥80 at baseline (Month 2).'}], 'classes': [{'title': 'Baseline', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.2', 'spread': '0.95', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Week 4', 'denoms': [{'units': 'Participants', 'counts': [{'value': '29', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.1', 'spread': '0.69', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 3', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.0', 'spread': '0.40', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 6', 'denoms': [{'units': 'Participants', 'counts': [{'value': '28', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.1', 'spread': '0.70', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.1', 'spread': '0.56', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 18', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.1', 'spread': '1.00', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.2', 'spread': '0.74', 'groupId': 'OG000'}]}]}, {'title': 'Change from Baseline Month 30', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.8', 'spread': '0.81', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and up to 84 months', 'description': 'Z-scores of Head Circumference determined using World Health Organization(WHO) growth charts for children \\<24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months and older.\n\nA head circumference z-score is a standardized head circumference measure after considering important factors like age and gender, in which higher z-scores are associated with children with larger heads. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of SD unit above the 50%; and a negative value is a factor of SD unit below 50%.', 'unitOfMeasure': 'Z-score change from baseline', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population, subjects less than 36 months of age.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Bayley-III Scores - Neurocognitive Testing Results', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sapropterin Dihydrochloride', 'description': 'A dose of 20 mg/kg dissolved in water or apple juice, administered once daily orally, with food.\n\nPart 2 (7 years): Sixty-five of the 71 subjects that were determined to be Kuvan responders in Part 1 were enrolled in Part 2. All 65 subjects met the minimum required IQ test score of ≥80 at baseline (Month 2).'}], 'classes': [{'title': 'Cognitive: Baseline', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '102.31', 'spread': '9.081', 'groupId': 'OG000'}]}]}, {'title': 'Cognitive: Change from Baseline Month 6', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '5.68', 'spread': '10.943', 'groupId': 'OG000'}]}]}, {'title': 'Cognitive: Change from Baseline Month 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '2.11', 'spread': '13.157', 'groupId': 'OG000'}]}]}, {'title': 'Cognitive: Change from Baseline Month 18', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '2.27', 'spread': '20.170', 'groupId': 'OG000'}]}]}, {'title': 'Cognitive: Change from Baseline Month 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.83', 'spread': '23.962', 'groupId': 'OG000'}]}]}, {'title': 'Language: Baseline', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '100.73', 'spread': '12.914', 'groupId': 'OG000'}]}]}, {'title': 'Language: Change from Baseline Month 6', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '2.59', 'spread': '10.966', 'groupId': 'OG000'}]}]}, {'title': 'Language: Change from BaselineMonth 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '1.37', 'spread': '14.469', 'groupId': 'OG000'}]}]}, {'title': 'Language: Change from Baseline Month 18', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '4.82', 'spread': '22.903', 'groupId': 'OG000'}]}]}, {'title': 'Language: Change from Baseline Month 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-3.00', 'spread': '18.407', 'groupId': 'OG000'}]}]}, {'title': 'Motor: Baseline', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '104.96', 'spread': '11.837', 'groupId': 'OG000'}]}]}, {'title': 'Motor: Change from Baseline Month 6', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '1.32', 'spread': '10.952', 'groupId': 'OG000'}]}]}, {'title': 'Motor: Change from Baseline Month 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '2.11', 'spread': '12.297', 'groupId': 'OG000'}]}]}, {'title': 'Motor: Change from Baseline Month 18', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.18', 'spread': '19.894', 'groupId': 'OG000'}]}]}, {'title': 'Motor: Change from Baseline Month 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '7.50', 'spread': '18.512', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'At Month 6, 12, 18 and 24', 'description': 'The Bayley-III is a tool for assessing all facets of development in infants within an age range of 12 to 30 months, with normative data available for infants as young as 16 days. Composite scores are derived for cognitive, language, and motor development and scaled to a metric, with a range of 40 to 160. Higher scores are a better outcome.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population, analysis only comprised of subjects less than 30 months of age.'}, {'type': 'SECONDARY', 'title': 'Baseline Concentration of Tetrahydrobiopterin (BH4)(C0)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '80', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sapropterin Dihydrochloride', 'description': 'A dose of 20 mg/kg dissolved in water or apple juice, administered once daily orally, with food.\n\nSubstudy 2 (Pharmacokinetics Substudy): 94 subjects participated in the PK substudy, one subject declined participation.'}], 'classes': [{'categories': [{'measurements': [{'value': '16.6', 'spread': '4.1', 'groupId': 'OG000'}]}]}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'At predose and postdose - 0.22, 3.2 and 7 hours', 'description': 'Baseline concentration of BH4(C0) with associated inter-individual variability.', 'unitOfMeasure': 'µg/L', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Eighty patients were evaluable from PKU-015 PK Sub-Study.'}, {'type': 'SECONDARY', 'title': 'Absorption Rate Constant (Ka) of Kuvan', 'denoms': [{'units': 'Participants', 'counts': [{'value': '80', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sapropterin Dihydrochloride', 'description': 'A dose of 20 mg/kg dissolved in water or apple juice, administered once daily orally, with food.\n\nSubstudy 2 (Pharmacokinetics Substudy): 94 subjects participated in the PK substudy, one subject declined participation.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.235', 'spread': '23.8', 'groupId': 'OG000'}]}]}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'At predose and postdose - 0.22, 3.2 and 7 hours', 'description': 'Population pharmacokinetic parameter, Absorption Rate Constant (Ka)', 'unitOfMeasure': 'l/hour', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Eighty subjects were evaluable from PKU-015 PK Sub-Study.'}, {'type': 'SECONDARY', 'title': 'Apparent Volume of Distribution (V/F) of Kuvan', 'denoms': [{'units': 'Participants', 'counts': [{'value': '80', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sapropterin Dihydrochloride', 'description': 'A dose of 20 mg/kg dissolved in water or apple juice, administered once daily orally, with food.\n\nSubstudy 2 (Pharmacokinetics Substudy): 94 subjects participated in the PK substudy, one subject declined participation.'}], 'classes': [{'categories': [{'measurements': [{'value': '1209', 'spread': '56.4', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'At predose and postdose - 0.22, 3.2 and 7 hours', 'description': 'Population pharmacokinetic parameter apparent volume of distribution (V/F)', 'unitOfMeasure': 'L', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Eighty subjects were evaluable from PKU-015 PK Sub-Study.'}, {'type': 'SECONDARY', 'title': 'Apparent Clearance (CL/F) of Kuvan', 'denoms': [{'units': 'Participants', 'counts': [{'value': '80', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sapropterin Dihydrochloride', 'description': 'A dose of 20 mg/kg dissolved in water or apple juice, administered once daily orally, with food.\n\nSubstudy 2 (Pharmacokinetics Substudy): 94 subjects participated in the PK substudy, one subject declined participation.'}], 'classes': [{'categories': [{'measurements': [{'value': '815', 'spread': '50.9', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'At predose and postdose - 0.22, 3.2 and 7 hours', 'description': 'Population pharmacokinetic parameter apparent clearance (CL/F)', 'unitOfMeasure': 'L/hour', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Eighty subjects were evaluable from PKU-015 PK Sub-Study.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Sapropterin Dihydrochloride', 'description': 'A dose of 20 mg/kg dissolved in water or apple juice, administered once daily orally, with food.\n\nPart 1: 95 subjects participated in Part 1.\n\nPharmacokinetic (PK) Sub-Study: 94 subjects participated in the PK substudy, one subject declined participation.\n\n6-month Safety/Efficacy Sub-Study: 65 subjects met the minimum required score of 80, Kuvan responders, all 65 subjects participated in Safety/Efficacy Substudy.\n\nPart 2: 65 subjects met the minimum required score of 80 at baseline (Month 2) neurocognitive tests, all 65 subjects participated in Part 2.'}], 'periods': [{'title': 'Part 1 (4 Weeks)', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '95'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '95'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}, {'title': 'PK Sub-Study 2 (4 Weeks)', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': '1 subject declined participation in the PK Sub-Study.', 'groupId': 'FG000', 'numSubjects': '94'}]}, {'type': 'COMPLETED', 'comment': 'of the 95 who started Part 1.', 'achievements': [{'groupId': 'FG000', 'numSubjects': '93'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'no postdose blood sample', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}, {'title': 'Safety/Efficacy Sub-Study 1 (6 Months)', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': '65 of 95 subjects in Part 1 were determined responders \\& eligible for the Safety/Efficacy Sub-study.', 'groupId': 'FG000', 'numSubjects': '65'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '63'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}]}]}, {'title': 'Part 2 (7 Years)', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': '65 of 95 subjects in Part 1 were determined responders \\& eligible for the Part 2 of the study.', 'groupId': 'FG000', 'numSubjects': '65'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '49'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '16'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}]}, {'type': 'Physician Decision', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'Sponsor Decision', 'reasons': [{'groupId': 'FG000', 'numSubjects': '6'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '5'}]}]}], 'recruitmentDetails': 'This was a multicenter study conducted at 20 sites in the U.S. and Canada.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '95', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Sapropterin Dihydrochloride', 'description': 'A dose of 20 mg/kg dissolved in water or apple juice, administered once daily orally, with food.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '3.2', 'spread': '1.94', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '57', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '38', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '6', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '89', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'categories': [{'title': 'Asian', 'measurements': [{'value': '5', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '79', 'groupId': 'BG000'}]}, {'title': 'Other', 'measurements': [{'value': '9', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Weight', 'classes': [{'categories': [{'measurements': [{'value': '15.6', 'spread': '6.08', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'kg', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Height', 'classes': [{'categories': [{'measurements': [{'value': '94.8', 'spread': '17.70', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'cm', 'dispersionType': 'STANDARD_DEVIATION'}], 'populationDescription': 'Safety Population consist of all subjects who received any study drug in the Full Analysis Set(FAS).'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2010-11-30', 'size': 10649052, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2020-08-14T12:14', 'hasProtocol': True}, {'date': '2019-04-26', 'size': 5080660, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2020-08-14T12:15', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 95}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2009-02'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-12', 'completionDateStruct': {'date': '2018-09-14', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-12-01', 'studyFirstSubmitDate': '2009-02-05', 'resultsFirstSubmitDate': '2020-08-14', 'studyFirstSubmitQcDate': '2009-02-05', 'lastUpdatePostDateStruct': {'date': '2020-12-22', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2020-12-01', 'studyFirstPostDateStruct': {'date': '2009-02-06', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2020-12-22', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2018-09-14', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Full-Scale Intelligence Quotient (FSIQ) Score', 'timeFrame': 'Assessments through 84 months.', 'description': 'Full Scale Intelligence Quotient (FSIQ) is a score derived through administration of selected subtests from age appropriate Wechsler Intelligence assessments. Weschler Preschool and Primary Scale of Intelligence (WPPSI)-III is used for children \\>30 months and ≤6 years; and Weschler Intelligence Scale for Children (WISC)-IV is used for children \\>6 years old. The outcome variable will be the FSIQ score from WPPSI-III and/or WISC-IV tests.\n\nFSIQ results can range from 40 being the lowest and 160 being the highest. Higher scores are associated with higher intelligence quotient.'}], 'secondaryOutcomes': [{'measure': 'Number of Subjects With Adverse Events (AEs)', 'timeFrame': 'Up to 7 years', 'description': 'Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, and that does not necessarily have a causal relationship with this treatment.\n\nDrug Related Adverse all noxious and unintended responses to a medical product related to any dose. This means that a causal relationship between a medicinal product and an AE is at least a reasonable possibility, ie, the relationship cannot be ruled out.\n\nA serious adverse event (SAE) is an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.'}, {'measure': 'Change From Baseline in Growth Measurements - Height Z-Scores', 'timeFrame': 'Baseline and up to 84 months', 'description': 'Z-scores of Height determined using World Health Organization(WHO) growth charts for children \\<24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months and older.\n\nA height z-score is a standardized height measure after considering important factors like age and gender, in which higher z-scores are associated with taller children. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of standard deviation (SD) unit above the 50%; and a negative value is a factor of SD unit below 50%.'}, {'measure': 'Change From Baseline in Growth Measurements - Weight Z-Scores', 'timeFrame': 'Baseline and up to 84 months', 'description': 'Z-scores of Weight determined using World Health Organization(WHO) growth charts for children \\<24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months or older.\n\nA weight z-score is a standardized weight measure after considering important factors like age and gender, in which higher z-scores are associated with heavier children. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of SD unit above the 50%; and a negative value is a factor of SD unit below 50%.'}, {'measure': 'Change From Baseline in Growth Measurements - Head Circumference Z-Scores', 'timeFrame': 'Baseline and up to 84 months', 'description': 'Z-scores of Head Circumference determined using World Health Organization(WHO) growth charts for children \\<24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months and older.\n\nA head circumference z-score is a standardized head circumference measure after considering important factors like age and gender, in which higher z-scores are associated with children with larger heads. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of SD unit above the 50%; and a negative value is a factor of SD unit below 50%.'}, {'measure': 'Change From Baseline in Bayley-III Scores - Neurocognitive Testing Results', 'timeFrame': 'At Month 6, 12, 18 and 24', 'description': 'The Bayley-III is a tool for assessing all facets of development in infants within an age range of 12 to 30 months, with normative data available for infants as young as 16 days. Composite scores are derived for cognitive, language, and motor development and scaled to a metric, with a range of 40 to 160. Higher scores are a better outcome.'}, {'measure': 'Baseline Concentration of Tetrahydrobiopterin (BH4)(C0)', 'timeFrame': 'At predose and postdose - 0.22, 3.2 and 7 hours', 'description': 'Baseline concentration of BH4(C0) with associated inter-individual variability.'}, {'measure': 'Absorption Rate Constant (Ka) of Kuvan', 'timeFrame': 'At predose and postdose - 0.22, 3.2 and 7 hours', 'description': 'Population pharmacokinetic parameter, Absorption Rate Constant (Ka)'}, {'measure': 'Apparent Volume of Distribution (V/F) of Kuvan', 'timeFrame': 'At predose and postdose - 0.22, 3.2 and 7 hours', 'description': 'Population pharmacokinetic parameter apparent volume of distribution (V/F)'}, {'measure': 'Apparent Clearance (CL/F) of Kuvan', 'timeFrame': 'At predose and postdose - 0.22, 3.2 and 7 hours', 'description': 'Population pharmacokinetic parameter apparent clearance (CL/F)'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Phenylketonuria', 'PKU', 'Kuvan', 'Phenoptin', 'Biopten', 'Neurocognitive Function', 'Phenylalanine'], 'conditions': ['Phenylketonuria']}, 'descriptionModule': {'briefSummary': 'This multicenter, open label study is designed to evaluate the safety of Kuvan® and its effect on neurocognitive function, blood Phe concentration, and growth in children with PKU who are 0-6 years old.', 'detailedDescription': 'Rigorous control of diet is typically advocated in children 4 years and under with PKU because brain sensitivity to high Phe concentrations is expected to be greatest during these years of rapid neurocognitive development.\n\nProlonged high blood Phe concentrations are neurotoxic and lead to impairment of intelligence and other brain functions (such as attentiveness). Reduction of blood Phe concentrations through dietary control is an important determinant of long-term neurologic outcome in PKU patients, and reduction of blood Phe concentrations in patients with PKU has been shown to decrease the long term risk of neurologic injury.\n\nIt is difficult for many patients to maintain reduced blood Phe, and many patients with PKU experience some degree of neurological impairment despite efforts to maintain dietary Phe control.\n\nThe strongest determinant of intelligence quotient (IQ) and cognitive function is compliance with blood Phe control. Several clinical studies with Kuvan have already demonstrated efficacy in reducing blood Phe in subjects older than 4 years. This study will examine whether addition of Kuvan to the standard of care at an early age in children with well controlled diets can lower blood Phe levels (ie, reach and maintain a goal of ≤ 240 micromole/L) and preserve neurocognitive functioning. In addition, this study will provide data on Kuvan exposure, rate of uptake, half life, and clearance in young children.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '6 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Established diagnosis of PKU with hyperphenylalaninemia (HPA) documented in the medical record by at least 2 blood Phe concentrations greater than or equal to 360 micromole/L (6 mg/dL) taken at least 3 days apart\n* Documented blood Phe control (defined by the standard used at each treatment center) prior to study enrollment, if applicable (eg, the subject is old enough for these data to be collected); blood Phe concentrations for subjects \\< 6 months old at Screening must be considered controlled and stable by the Investigator\n* Willing to adhere to a prescribed Phe restricted diet in order to maintain blood Phe concentrations within the recommended ranges established at the subject's study site\n* Age 0 to 6 years old, inclusive, at Screening\n* Parent(s) or guardian(s) willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures\n* Parent(s) or guardian(s) willing and able to comply with all study procedures\n* Female subjects of childbearing potential (as determined by the investigator) and sexually mature male subjects willing to use a medically accepted method of contraception throughout the study. Female subjects of childbearing potential willing to undergo periodic pregnancy tests during the course of the study\n\nExclusion Criteria:\n\n* Established diagnosis of primary tetrahydrobiopterin (BH4) deficiency\n* Known hypersensitivity to Kuvan or its excipients\n* History of organ transplantation\n* Perceived to be unreliable or unavailable for study participation or to have parents or legal guardians who are perceived to be unreliable or unavailable\n* Use of methotrexate or other medications that inhibit folate metabolism\n* Serious neuropsychiatric illness (eg, major depression) not currently under medical control\n* Use of Kuvan or any investigational agent within 30 days prior to Screening, or known requirement for any investigational agent prior to completion of all scheduled study assessments\n* Concurrent disease or condition that would interfere with study participation or safety (eg, seizure disorder, oral steroid-dependent asthma or other condition requiring oral or parenteral corticosteroid administration, or insulin dependent diabetes)\n* Any condition that, in the view of the Principal Investigator (PI), renders the subject at high risk for failure to comply with treatment or to complete the study\n* Use of phosphodiesterase type 5 (PDE5) inhibitor."}, 'identificationModule': {'nctId': 'NCT00838435', 'acronym': 'PKU-015', 'briefTitle': 'Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU', 'organization': {'class': 'INDUSTRY', 'fullName': 'BioMarin Pharmaceutical'}, 'officialTitle': 'A Phase 3b Open-Label Study to Evaluate the Effect of Kuvan® on Neurocognitive Function, Maintenance of Blood Phenylalanine Concentrations, Safety, and Population Pharmacokinetics in Young Children With Phenylketonuria', 'orgStudyIdInfo': {'id': 'PKU-015'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'sapropterin dihydrochloride', 'description': "A dose of 20 mg/kg will be administered dissolved in water or apple juice, based on subject's age and ability, and taken orally once daily with food.", 'interventionNames': ['Drug: sapropterin dihydrochloride']}], 'interventions': [{'name': 'sapropterin dihydrochloride', 'type': 'DRUG', 'otherNames': ['Kuvan', 'Phenoptin', 'BH4', '6R BH4'], 'description': "A dose of 20 mg/kg will be administered dissolved in water or apple juice, based on subject's age and ability, and taken orally once daily with food.", 'armGroupLabels': ['sapropterin dihydrochloride']}]}, 'contactsLocationsModule': {'locations': [{'city': 'La Jolla', 'state': 'California', 'country': 'United States', 'geoPoint': {'lat': 32.84727, 'lon': -117.2742}}, {'city': 'Orange', 'state': 'California', 'country': 'United States', 'geoPoint': {'lat': 33.78779, 'lon': -117.85311}}, {'city': 'Tampa', 'state': 'Florida', 'country': 'United States', 'geoPoint': {'lat': 27.94752, 'lon': -82.45843}}, {'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'city': 'Kansas City', 'state': 'Missouri', 'country': 'United States', 'geoPoint': {'lat': 39.09973, 'lon': -94.57857}}, {'city': 'Cleveland', 'state': 'Ohio', 'country': 'United States', 'geoPoint': {'lat': 41.4995, 'lon': -81.69541}}, {'city': 'Columbus', 'state': 'Ohio', 'country': 'United States', 'geoPoint': {'lat': 39.96118, 'lon': -82.99879}}, {'city': 'Hershey', 'state': 'Pennsylvania', 'country': 'United States', 'geoPoint': {'lat': 40.28592, 'lon': -76.65025}}, {'city': 'Nashville', 'state': 'Tennessee', 'country': 'United States', 'geoPoint': {'lat': 36.16589, 'lon': -86.78444}}, {'city': 'Salt Lake City', 'state': 'Utah', 'country': 'United States', 'geoPoint': {'lat': 40.76078, 'lon': -111.89105}}, {'city': 'Milwaukee', 'state': 'Wisconsin', 'country': 'United States', 'geoPoint': {'lat': 43.0389, 'lon': -87.90647}}, {'city': 'Edmonton', 'state': 'Alberta', 'country': 'Canada', 'geoPoint': {'lat': 53.55014, 'lon': -113.46871}}, {'city': 'Vancouver', 'state': 'British Columbia', 'country': 'Canada', 'geoPoint': {'lat': 49.24966, 'lon': -123.11934}}, {'city': 'Winnipeg', 'state': 'Manitoba', 'country': 'Canada', 'geoPoint': {'lat': 49.8844, 'lon': -97.14704}}, {'city': 'Hamilton', 'state': 'Ontario', 'country': 'Canada', 'geoPoint': {'lat': 43.25011, 'lon': -79.84963}}, {'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'city': 'Montreal', 'state': 'Quebec', 'country': 'Canada', 'geoPoint': {'lat': 45.50884, 'lon': -73.58781}}, {'city': 'Sainte-Foy', 'state': 'Quebec', 'country': 'Canada', 'geoPoint': {'lat': 46.78139, 'lon': -71.29217}}], 'overallOfficials': [{'name': 'Joshua Lilienstein, M.D.', 'role': 'STUDY_DIRECTOR', 'affiliation': 'BioMarin Pharmaceutical'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'BioMarin Pharmaceutical', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}